The mRNA-based vaccines cannot lead to COVID-19 or its symptoms since they only lead to the production of the spike protein in the cell.

However, the spike protein itself can lead to cell fusion: Quantitative assays reveal cell fusion at minimal levels of SARS-CoV-2 spike protein and fusion from without

Is this a potential risk of the mRNA vaccine ? I could imagine, that the spike protein needs to be bound to the virus to induce this effect ? I could not find any literature where the effect of the unbound spike protein is tested.

  • $\begingroup$ Why the down vote ? $\endgroup$
    – Felix Z.
    Commented Feb 23, 2021 at 23:11
  • $\begingroup$ The virus membrane anchored spike provokes virion-cell fusion, the cell membrane anchored spike provokes cell-cell fusion, when encountering ACE2. In most vaccines the 2P mutation greatly reduces this behavior (not in the AstraZeneca vaccine). $\endgroup$
    – reuns
    Commented Feb 27, 2021 at 14:04

1 Answer 1


The mRNA vaccines encode a mutant version of the spike protein in which the structural transition needed to to fuse membranes is blocked. This was done to make the immune response focus on the pre-fusion state, which is much better for neutralizing the virus.

From https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behind-COVID-19/98/i38:

Fortuitously, Graham and a former postdoc, Jason McLellan, devised a solution to this problem before the pandemic. Through a bit of structural biology and persistent protein engineering, McLellan discovered that adding two prolines—the most rigid of the 20 amino acids—to a key joint of a vaccine’s spike protein could stabilize the structure’s prefusion shape. This 2P mutation worked in preclinical studies of Graham and Moderna’s MERS vaccine, so they applied it to Moderna’s COVID-19 vaccine.

I don't know if cells expressing wild-type spike protein would fuse into syncytia, but it seems very unlikely to happen with the vaccine spike.

  • $\begingroup$ Comments are not for extended discussion; this conversation has been moved to chat. $\endgroup$
    – Bryan Krause
    Commented May 4, 2021 at 21:41

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